Neural responses are noisy. Yet behavior is remarkably accurate and precise. How is this accomplished? Is variation in neural responses simply noise that needs to be reduced? Or is it an important signal that is used to control behavior and learning? The seven projects in this application for a Conte Center for Neuroscience Research (CCNR) will ask how neural variation is used to drive behavior, determining where noise falls on the continuum from being a detriment for brain function, neutral, or an asset. The responses of a group of neurons for a given stimulus or action is called a "central representation", and these exist throughout the brain for processing complex sensory stimuli, or planning and executing complex movements. The cerebral cortex has particularly variable neural codes, yet has been widely implicated in guiding normal performance and learning for both sensation and action. This CCNR has the long-term goal of understanding the role of variation as a component of the neural code in the cortex and related areas of the basal ganglia. A related long-term goal is to understand how abnormal variation contributes to failures of adaptation, reductions in the precision and accuracy of behavior, and ultimately to the symptoms of neuro-behavioral and neuro- psychiatric disorders. The seven projects have three center-wide specific aims. First, they will characterize the variation in specific neural codes and behaviors and divide the variation into the component that is related to behavior and one that comprises unrelated, or "residual", variation. Second, they will ask whether natural modes of neural modulation such as attention and reward, or chemical modulatory systems, alter neural variation, and thereby behavior. Third, they will investigate the relationship between changes in neural variation and behavioral learning, seeking cause-and-effect relationships. The seven projects will ask these questions on six different behaviors: smooth pursuit eye movements, reaching arm movements, bird song, spatial behavior, auditory processing, and categorization of speech sounds. They will use species including rodents, songbirds, non-human primates, and humans. The ultimate goal of the CCNR will be to understand the relationship between neural variation and normal behavior to enable creation of behavioral and chemical therapies for treating and curing neuro-behavioral disorders.